This action might not be possible to undo. Are you sure you want to continue?
Study: ³Cerebrospinal Fluid Treponemal Antibodies in Untreated Early Syphilis´
Montana Whitington, Santa Clara, CA 95050, Microbiology 113
Treponemapallidumpallidum is a motile spirochete bacteria and the causative agent of Syphilis disease. It is acquired by close sexual contact (chafed skin/mucous membranes) or transmitted to a fetus via transplacental passage. There is no vaccine for syphillis as T. pallidum, along with many other treponeme bacteria, does not have enough surface proteins for an antibody to be effective. The diagnostic tests for syphilis vary in reliability. The stage of syphilis (primary, secondary, latent, tertiary) significantly affects the likelihood of receiving a correct +/- syphilis diagnostic test. Syphilis in some stages is asymptomatic thus clinical diagnosis must be supported by extensive lab tests which often present false negatives, false positives, or inconclusive results. The nature of the bacterium makes it difficult to detect in untreated syphilis patients, and the diagnosis of neurosyphilis especially difficult. Invasion of the CNS by the bacterium can occur at any stage of the disease and presents permanent debilitating effects in untreated patients. In the pre-antibiotic era, the CSF criteria to establish a diagnosis of asymptomatic neurosyphilis was varied and inconsistent. Since then, there is still no consensus regarding a definitive diagnosis of a patient with asymptomatic neurosyphilis.Pre-penicillin era syphilis patients were subject to treatment using Salvasaran or other arsenic-containing drugs or mercury, neither of which were 100% effective. Current treatment includes a drug regimen of penicillin¶s and differs respective of disease stage, making diagnosis very significant in the treatment of a syphilitic patient.
Results. 3. LATENT/DORMANT
May have no symptoms for years or ever again, or enter tertiary. No lesions present. 1. Of the 39 patients, 8 had reactive CSF-VDRL and are categorized as definite neurosyphilis. 2. Those patients with possibleneurosyphilis (n=11) had mildly elevated cell count or protein concentration and a nonreactive CSF-VDRL. 3. Patients (n=20) with normal cell count and protein concentration, non-reactive CSF-VDRL, were considered normal. Only moderate agreement between CSF MHA-TP and CSF FTA-ABS tests were found. The CSF MHA-TP test was more likely to be reactive due to the more rigid criteria required for a CSF FTA-ABS to be reactive (MHA-TP: any degree of agglutination is reactive, versus on a 0-4 scale of fluorescence the FTA-ABS must get a 2 or more to be reactive.
2 weeks-3months after chancre the organisms invade every organ and body fluid. Clinical manifestations include rough rashes on palms of hand/soles of feet, fever, swollen lymph nodes, sore throat, headache, arthritis, possible hepatitis or meningitis, and wart-like sores called condylomalatum.
Serologic tests reactive in early latent stage. Nontreponemal tests reactivity decreased with increasing latency. Syphilitic infection of the nervous system results in chronic meningeal inflammation and occurs in persons with untreated syphilis. CNS invasion can occur at any stage of syphilis.
Figure 1.Photograph of T. pallidum showing
spirochete morphology. It moves in a corkscrew motion through the mucus. It is not seen on a gram stain because it is too thin.
Vital organs are attacked, leads to dementia, paralysis, blindness. Classified into three categories: gummatous, cardiovascular, or neurosyphilis. Complications lead to death
1. Nontreponemal serologic test to initially screen. a) VDRL slide test: Not sensitive in primary and late. Measure immunoglobin M (IgM) and IgG antibodies to lipoidal material released from damaged host cells as well as lipoprotein- like material and cardiolipin released from treponemes. The antilipoidal anti bodies are produced not only as a consequence of syphilis and other treponemal diseases, but also as a result of other diseases in which tissue damage occurs. Thus, without other evidence of syphilis diagnosis a reactive nontreponemal test does not confirm T. pallidum infection. 2. Treponemalserologic tests use T. pallidumas the antigen and detect antibodies directed against treponemal components. Used to verify reactivity in the non-treponemal tests. a) MHA-TP b) FTA-ABS
Results for ~30% of patients with late syphilis are nonreactive in nontreponemal tests. Treponemal tests are almost always reactive. Lesions (gummas) of benign late syphilis have few treponemes present by direct microscopic examination.
10-90 days after exposure will see clinical symptoms of enlarged groin lymph nodes and visible chancre (painless sore).
Cerebrospinal Fluid Treponemal Antibodies in Untreated Early Syphilis.
This study examines the diagnostic utility of cerebrospinal fluid (CSF) treponemal antibodies and the prevalence of these antibodies in early syphilis.
Direct Microscopic Examination of Lesions: Best during primary and secondary stages when moist lesions (chancres, condylomatalatum, or mucous patches) with large numbers of treponemes are present. Specimen source not available in latent and late stages since lesions not present. However, other treponeme species must be excluded as the cause of infection.
Materials and Methods.
40 patients with untreated primary and secondary syphilis. Each underwent lumbar puncture and 15 were HIV sero-positive, the rest HIV sero-negative. Patients with primary syphilis have 1+ chancres. Patients with secondary syphilis had condylomatalataor the typical rash. All had reactive serum VDRL tests. No patient had health problems other than HIV or syphilis that might produce CSF abnormalities. Figure 4. The proportion of patients in each CSF group with
CSF treponemal antibodies.
If the nonreactive CSF treponemal tests are used to exclude neurosyphilis diagnosis in patients with possible neurosyphilis, 3/10 would be excluded by the CSF MHA-TP test and 7/11 would be excluded by the FTA-ABS test.
A gold standard does not exist in the assessment of syphilis or asymptomatic neurosyphilis. It is impractical to isolate T. pallidum from the CSF and sensitivity to this bacteria is best only in the early courses of CNS invasion. CSF-VDRL is a very specific, but insensitive test. A negative result to this test should never exclude a positive diagnosis. Thus, use of the CSF-MHA-TP test, which gives the most conservative estimate of patients without neurosyphilis but with syphilis, should be used to exclude neurosyphilis diagnosis. The stage of the disease significantly effects diagnostic accuracy as well as treatment methods, making it difficult to treat a patient with an unknown history or extended period without treatment. For now, it is necessary for clinicians to perform repeat tests and various diagnostic techniques in order to make an true syphilis diagnosis.
Figure 2. DFA (Direct
Fluorescent Antibody) Stain is used in the dark-field microscopic detection method. This is the most reliable method of diagnosing primary and secondary syphilis.
Figure 3. Both FTA-ABS and and MHA-TP tests show the least amount of
reactive cases in confirmed syphilis cases during the primary and late syphilis stages. During the secondary stage, both have the highest percent of correct positive tests.
Marra, Christina, M, MD, Critchlow, Cathy W. PhD, Hook, Edward W. III, Collier, Ann C., Lukehart, Sheila, A. Cerebrospinal Fluid Treponemal Antibodies in Untreated Early Syphilis. Arch Neurology.http:// archneur.amaassn.org/cgi/reprint/52/1/68>. 29 NOV 2010. 52: 68-72. Larsen, Sandra A., Steiner, Bret M, Rudolph Andrew H. Laboratory Diagnosis and Interpretation of Tests fr Syphilis. Clinical Microbiology Reviews. Jan 1995. 8:1-21.